Lipid peroxidation products are early stage and major mediators in the inflammatory cascade. These products include endogenous and/or exogenous aldehydes, such as 4-hydroxy-nonenal, malondialdehyde and acrolein and act by stable modification of proteins, which subsequently alter their stability and functionality upon adduct formation. Several diseases have been shown to be associated with or caused by enhanced adduct formation with aldehydes, including neurodegenerative diseases (Alzheimer, Parkinson), atherosclerosis, osteoarthritis, cataract etc.
Aldehyde and keto groups are reactive electrophiles. They will react with nucleophiles, preferentially nucleophiles containing nitrogen having a free electron pair, to form Schiff bases or imine derivatives. Subsequent rearrangement e.g. of the Amadori type, may produce a new aldehyde or keto group susceptible to reaction with yet another nucleophile. This forms the basis of protein cross-linking and subsequent denaturation.
Another in vivo aldehyde modification is the reaction of amino groups, e.g. in proteins, with carbohydrates having a reducing end with a masked aldehyde functionality. This non-enzymatic glycation produces “Advanced Glycation End products” also called AGE modifications of proteins that potentially may lead to inflammation. These reactions are related to the Maillard reaction.
Several molecules, including carnosine hydralazine etc, exhibit aldehyde scavenging properties in vitro, by trapping the aldehyde as an imine or Schiff base, but the effects are questionable or sparse when applied in vivo and in a clinical setting. The foremost reason for a limited aldehyde scavenger effect is the small sizes of these molecules which give them an unfavourable pharmacokinetic profile.
It is believed that the active principle of the inventive composition is capable of mitigating the effects an early stage mediator might have on an inflammatory-related response due to its content of reactive groups which are capable of forming covalent binding with an electrophilic carbonyl group and/or an electrophilic carbon-carbon multiple bond. The carbonyl group is in particular believed to be an aldehyde group which possibly is conjugated with a carbon-carbon multiple bond (α,β-unsaturation). Our results suggest that the favourable effect found requires the factual formation of covalent binding between our active principle and an early stage mediator via the reactive groups indicated. However, since this hasn't yet been finally confirmed, the invention is for the time being (at the filing of this specification) not linked to such a mechanism. There may still be other explanations for the favourable and surprising effects we have accomplished with our active principle containing selected carrier-bound reactive nucleophilic groups.
The invention is concerned with two main kinds of mediators giving raise to inflammatory-related responses:
a) Endogenous mediators are formed in the individual where they exert their effects. This group includes as one subgroup mediators/substances which are part of a response leading to inflammation and as a second subgroup mediators/substances which are capable of causing undesired effects which can be considered as part of an inflammatory-related response but not necessarily as inflammation, e.g. discomfort, head-ache, hangover, cataract etc., and                b) Exogenous mediators are formed outside the individual where they exert their effects. They are capable of causing an inflammatory-related effect in vivo, and/or have to be transformed in vivo to an endogenous mediator before such an effect can be accomplished.        
Inflammatory-related conditions (as well as inflammatory-related reactions and effects) will in the context of the invention encompass inflammation as well as the undesired conditions discussed in the preceding paragraphs if not otherwise indicated.
Illustrative scientific articles and patent documents concerning aldehyde containing mediators and/or scavenging of such mediators are:    1. Burcham et al., WO 2003055487 Method of controlling damages mediated by α,β-unsaturated aldehydes.    2. Burcham et al., WO 2006002473 Method of controlling damages mediated by unsaturated aldehydes.    3. Cho et al., WO 2009091992 Repairing damaged nervous system tissue with nanoparticles.    4. Guitto et al., Synthesis and evaluation of neuroprotective α,β-unsaturated aldehyde scavenger histidyl-containing analogues of carnosine. J. Med. Chem. 48 (2005) 6156-6161.    5. Guitto et al., Malondialdehyde scavenging and aldose-derived Schiffs bases' transglycosylation properties of synthetic histidyl-hydrazide carnosine analogs. Bioorg. Med. Chem. 15 (2007) 6158-6163.    6. Hamann et al., Hydralazine inhibits compression and acrolein-mediated injuries in ex vivo spinal cord. J. Neurolog 104 (2008) 708-718    7. Hamann et al., Acrolein scavenging: a potential novel mechanism of attenuating oxidative stress following spinal cord injury. J. Neurochem 111 (2009) 1348-1356.    8. Ito et al., Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone. Biomaterials 28 (2007) 178-1786.    9. Monnier et al., Wake up and smell the Maillard reaction. Sci. Aging Knowl. Environ. 50 (2002) pe21    10. Negre-Salvayre et al., “Review: Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br. J. Pharmacol. 153 (2008) 6-20    11. Reddy et al., Carnosine: a versatile antioxidant and antiglycating agent. Sci. Aging Knowl. Environ. 18 (2005) pe12
The synthesis and use of polymers exhibiting covalently attached aldehyde-reactive functionalities or aldehyde groups have been described in WO 2009108100 (IPR-Systems AB) and references cited therein. The publication indicates that the hydrogel formed by reactiion of these two differently functionalized polymers with each other in vivo may be highly biocompatible causing low or no host defence reaction including low or no inflammation. Nothing has been concluded about the reason for this.